Genotype-Tissue Expression (GTEx) Project
Genotype-Tissue Expression Project The Genotype-Tissue Expression Project is a database and accompanying tissue bank intended for the scientific community to study the relationship between gene expression and genetic variation in human tissue. Through genome wide association studies or GWAS there have been many strong statistical links made between common genetic variations at thousands of different gene locations and upwards of 250 human traits. However, the mechanisms behind most of these variations are still unknown. Due to the fact that roughly 90% of the loci associated with these variants are located outside of protein-coding sequence, it is thought that a large number of the variations play rolls in gene regulation. In order to study the genetic basis of common disease, it is essential to study the relationships GWAS have discovered.1 A technique called expression quantitative trait locus (eQTL) mapping is being used to decipher these GWAS relationships. eQTL's are genome wide loci that control the expression levels of mRNAs. These expressive traits are different from other complex traits because the mRNA or protein trait is usually the product of one gene at a certain location within a chromosome. The mapping of these loci produces an estimated location of these variants gene-of-origin. Studies done on skin, adipose, brain, blood and liver have demonstrated that humans have many eQTLs. However, the regulation of gene expression is different between tissues and quite a number of human traits are only expressed in a certain set of cell types or at a specific time in development.1 Connecting data from eQTL mapping with data on molecular phenotypes and then linking that to known DNA sequences is an extremely successful way to study gene regulation across multiple tissues. In order to do this, biological information on human tissue must be ascertained from tissue samples. Unfortunately, human biospecimens are extremely hare to come by from living specimens, in particular pancreas, heart and brain samples. Due to this, the majority of studied eQTL's have been on RNA from a few sampled tissues or immortalized lymphoblasts or lymphocytes.1 The Design of the Project In order to move forward with the the studies of the links between genetic variation in human tissues and gene expression, it would be extremely helpful to establish a database of blood samples from genotyped individuals. This would provide researchers with a way to search for eQTL's and connect them to disease-associated variants from sequencing or GWAS studies. By adding more molecular phenotypes to this database, it would further our knowledge of the link between gene expression and genetic variation at a epigenetic and proteomic level. In response to this, a NIH workshop was held in June 2008 to discuss the matter and the GETx project was the product.1 The initial phase of the GTEx project was a 2.5-year period in which an autopsy program yielding high-quality nucleic acids and a high quantity of gene expression measurements. It is expected that the project will reach 900 post-mortem donors by the end of 2015. Post-mortem autopsy tissue and organ samples, skin fat and muscle samples often discarded during surgery, as well as blood samples are used as the biospecimens the data is collected from. Through sequencing and gene expression array, eQTL's have been identified and made available to the scientific community through the GTEx data portal.1 Reference 1 John Lonsdale, J. T., Mike Salvatore, Rebecca Phillips, Edmund Lo, Saboor Shad, Richard Hasz, Gary Walters, Fernando Garcia, Nancy Young, Barbara Foster, Mike Moser, Ellen Karasik, Bryan Gillard, Kimberley Ramsey, Susan Sullivan, Jason Bridge, Harold Magazine, John Syron, Johnelle Fleming, Laura Siminoff, Heather Traino, Maghboeba Mosavel, Laura Barker, Scott Jewell et al. (2013). The Genotype-Tissue Expression (GTEx) Project NAture Genetics 45, 580-585. 2 http://www.genenetwork.org/webqtl/main.py?FormID=sharinginfo&GN_AccessionId=545